Process for manufacturing integrated chemical microreactors of semiconductor material

ABSTRACT

The microreactor is completely integrated and is formed by a semiconductor body having a surface and housing at least one buried channel accessible from the surface of the semiconductor body through two trenches. A heating element extends above the surface over the channel and a resist region extends above the heating element and defines an inlet reservoir and an outlet reservoir. The reservoirs are connected to the trenches and have, in cross-section, a larger area than the trenches. The outlet reservoir has a larger area than the inlet reservoir. A sensing electrode extends above the surface and inside the outlet reservoir.

TECHNICAL FIELD

[0001] The present invention refers to a process for manufacturingintegrated chemical microreactors of semiconductor material.

BACKGROUND OF THE INVENTION

[0002] As is known, the treatment of some fluids involves anincreasingly precise temperature regulation, in particular when chemicalor biochemical reactions are involved. Furthermore, it is frequentlynecessary to use very small amounts of fluid, since the fluid is costlyor not always readily available.

[0003] This is, for example, the case of the DNA-amplification process(polymerase chain reaction process, also called a PCR process) whereinprecise temperature control in the various phases (it is necessary torepeatedly perform preset thermal cycles), the need to avoid as far aspossible thermal gradients in the reaction areas of the fluid (to haveuniform temperature in these areas), and also the quantity of fluid used(which is very costly) are of crucial importance for obtaining goodreaction efficiency or even for obtaining the reaction itself.

[0004] Other examples of treatment of fluids having the characteristicsindicated above are, for instance, linked chemical and/orpharmacological analyses, biological tests, etc.

[0005] At present, various techniques are available that enable thermalcontrol of chemical or biochemical reagents. A first technique uses areactor including a glass or plastic base on which a biological fluid isdeposited through a pipette. The base rests on a hot-plate called“thermo-chuck,” which is controlled by external instrumentation.

[0006] Another known reactor comprises a heater, which is controlled byappropriate instrumentation and on which a biological fluid to beexamined is deposited. The heater is supported by a base which alsocarries a sensor arranged in the immediate vicinity of the heater and isalso connected to the instrumentation for temperature regulation, so asto enable precise control of the temperature.

[0007] Both types of reactors are often enclosed in a protective casing.

[0008] A common disadvantage of the known reactors lies in the largethermal mass of the system; consequently, they are slow and have highpower absorption. For example, in the case of the PCR process mentionedabove, times of the order of 6-8 hours are required.

[0009] Another disadvantage of known solutions is linked to the factthat, given the macroscopic dimensions of the reactors, they are able totreat only relatively high volumes of fluids (i.e., minimum volumes ofthe order of milliliters).

[0010] The disadvantages referred to above result in very high treatmentcosts (in the case of the aforementioned PCR process, the cost canamount to several hundreds of dollars); in addition, they restrict therange of application of known reactors to test laboratories alone.

[0011] To overcome the above mentioned drawbacks, starting from the lateeighties miniaturized devices of reduced thermal mass have beendeveloped and allow a reduction in the times required for completing theDNA-amplification process.

[0012] The first of these devices is described in the article by M. A.Northrup, M. T. Ching, R. M. White, and R. T. Watson, “DNA amplificationwith a microfabricated reaction chamber,” Proc. 1993 IEEE Int. Conf.Solid-State Sens. Actuators, pp. 924-926, 1993, and comprises a reactorcavity formed in a substrate of monocrystalline silicon by anisotropicetching. The bottom of the cavity comprises a thin silicon-nitridemembrane, on the outer edge of which are heaters of polycrystallinesilicon. The top part of the cavity is sealed with a glass layer. Thanksto its small thermal mass, this structure can be heated at a rate of 15°C. /sec., with cycling times of 1 minute. With this device it ispossible to carry out, for a volume of fluid of 50 μl, twentyamplification cycles in periods approximately one fourth the timerequired by conventional thermocyclers and with a considerably lowerpower consumption.

[0013] However, the described process (as others currently used based onbonding of two silicon substrates previously subjected to anisotropicetches in KOH, TMAH, or other chemical solutions) is costly, has highcritical aspects and low productivity, and is not altogether compatiblewith the usual manufacture steps used in microelectronics.

[0014] Other more recent solutions includes forming, inside a firstwafer of semiconductor material, buried channels connected to thesurface via inlet and outlet trenches, and, inside a second wafer ofsemiconductor material, reservoirs formed by anisotropic etching, andbonding together of the two wafers.

[0015] Also this solution, however, is disadvantageous in that theprocess is costly, critical, has low productivity, and requires the useof a glass frit for bonding the two wafers together.

SUMMARY OF THE INVENTION

[0016] The aim of the present invention is therefore to provide aprocess allowing integration of reservoirs in a single integrated devicethat includes the chemical microreactor.

[0017] According to one embodiment of the invention, an integratedmicroreactor is provided, having a semiconductor material body, one ormore buried channels extending in the semiconductor material body at adistance from the surface, first and second trenches extending from thesurface respectively as far as first and second ends of the buriedchannels, and a resist layer extending above the surface and definingfirst and second reservoirs connected to the first and second trenches.

[0018] A process for the fabrication of an integrated microreactor isencompassed by the invention, including forming a semiconductor materialbody having one or more buried channels, forming first and secondtrenches extending from the surface of the semiconductor body as far as,respectively, first and second ends of the buried channels and formingfirst and second reservoirs above the surface, respectively connected tothe first and second trenches.

[0019] A method for the use of a microreactor is also described as partof the invention. The method includes introducing a fluid from areservoir into a reactor cavity, where the reactor cavity is a buriedchannel extending in a semiconductor material body at a distance from asurface of the semiconductor material body, where the reservoir isformed in a resist layer on the surface of the semiconductor materialbody, and where the fluid is introduced via a trench extending from thereservoir on the surface of the semiconductor material body as far asone end of the buried channel. Then heating the fluid within thereaction chamber, and cooling the fluid within the reaction chamber.This method may also include removal of the fluid from the reactionchamber into a second reservoir, also formed in the resist layer on thesurface of the semiconductor material body where the fluid may besampled by the use of a sensing electrode for the presence of a productof the method.

BRIEF DESCRIPTION OF THE DRAWINGS

[0020] For a better understanding of the present invention, twopreferred embodiments thereof are now described, simply as non-limitingexamples, with reference to the attached drawings, wherein:

[0021] FIGS. 1-5 show cross-sections through a wafer of semiconductormaterial in successive manufacturing steps of a microreactor accordingto a first embodiment of the invention;

[0022]FIG. 6 shows a top view of the wafer of FIG. 5;

[0023]FIGS. 7 and 8 show cross-sections similar to those of FIGS. 1-5,in final manufacturing steps; and

[0024] FIGS. 9-12 show cross-sections through a wafer of semiconductormaterial in successive manufacturing steps of a microreactor accordingto a second embodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION

[0025]FIG. 1 shows a wafer 1 comprising a semiconductor body 2,typically of monocrystalline silicon, accommodating buried channels 3extending parallel to a surface 4 of the semiconductor body 2.Preferably, as indicated in the top view of FIG. 6 by dashed lines, aplurality of buried channels 3 extend parallel to one another at shortdistances. In this case, the buried channels 3 may have an approximatelycircular or rectangular section and are arranged at a distance of 50 μmfrom one another and at a depth of 20-30 μm from the surface 4. When theburied channels 3 have a rectangular cross-section, they have an area of30 μm×200 μm, and a length of 10 mm, and the total area occupied by theburied channels 3 is 50 mm². Alternatively, it is possible to have asingle channel, approximately 10 mm in length, approximately 5 mm inwidth, and approximately 20 μm in height. In both cases, a total volumeis obtained of approximately 1 mm³ (1 μl).

[0026] A first insulating layer 5, for example of silicon dioxide,extends on top of the surface 4 of the semiconductor body 2 andaccommodates a polycrystalline-silicon heating element 10. Preferably,the heating element 10 extends substantially over the area occupied bythe buried channels 3, but not over the longitudinal ends of the buriedchannels 3, where inlet and outlet openings of the channels 3 are to beformed, as described hereinafter.

[0027] Contact regions 11, for example of aluminum, extend throughopenings of the first insulating layer 5 and are in electrical contactwith two opposite ends of the heating element 10 to enable passage ofelectric current through the heating element 10 and heating of theunderlying area.

[0028] A sensing electrode 12 formed by a multilayer, for example ofaluminum, titanium, nickel and gold, in a per se known manner and thusnot described in detail, extends on top of the first insulating layer 5,laterally shifted with respect to the buried channels 3.

[0029] A second insulating layer 13, for example of TEOS (tetra-ethylorthosilicate) oxide extends on top of the first insulating layer 5 andhas an opening through which the sensing electrode 12 protrudes.

[0030] The wafer 1 of FIG. 1 is obtained, for example, as describedbelow. Initially, the buried channels 3 are formed, preferably accordingto the teaching of European patent applications 99830206.1 of May 9,1999, and 00830098.0 of Feb. 11, 2000, filed by the present applicantand incorporated herein for reference. Initially, a substrate ofmonocrystalline silicon is time etched in TMAH to form the channels 3.Then the channels 3 are preferably coated with a material inhibitingepitaxial growth, and a monocrystalline epitaxial layer is grown on topof the substrate and of the channels. The epitaxial layer closes at thetop the buried channels 3 and forms, together with the substrate, thesemiconductor body 2 in which, if so envisaged, control electroniccomponents may be integrated at the sides of the buried channels.

[0031] Subsequently, and in succession, the following steps areperformed: the bottom portion of the first insulating layer 5 isdeposited on the surface 4; a polycrystalline silicon layer is depositedand defined so as to form the heating element 10; the top portion of thefirst insulating layer 5 is formed; openings are made in the firstinsulating layer 5; an aluminum layer is deposited and defined to formthe contact regions 11 and the bottom region of the sensing electrode12; the second insulating layer 13 is deposited and then removed fromthe area corresponding to the sensing electrode 12; and next thealuminum, titanium, nickel and gold regions forming the sensingelectrode 12 are formed.

[0032] Subsequently (FIG. 2), a protective layer 15 is formed. For thispurpose, a layer of standard positive resist may be deposited, forexample including three components, formed by a NOVOLAC resin, aphotosensitive material or “pac” (photo-active compound), and a solvent,such as ethylmethyl ketone and lactic acid, used normally inmicroelectronics for the definition of integrated structures.Alternatively, another compatible material may be used, which can bedefined and is capable of resisting etching both of the silicon of thesemiconductor body 2 and of the material still to be deposited on top ofthe protective layer 15, such as a TEOS oxide, in which case theprotective layer 15 blends with the second protective layer 13.

[0033] Next (FIG. 3), the protective layer 15 is defined and, where theprotective layer 15 has been removed, the second insulating layer 13 andfirst insulating layer 5 are etched. In this way, an inlet opening 16 aand an outlet opening 16 b are obtained that extend as far as thesurface 4 of the semiconductor body 2 and are basically aligned to thelongitudinal ends of the channels 3. The inlet opening 16 a and outletopening 16 b preferably have a length of approximately 5 mm (in adirection perpendicular to the plane of the drawing) and a width ofapproximately 60 μm.

[0034] A resist layer 18 is then deposited (FIG. 4), in the exampleillustrated the resist being negative and having a thermal conductivityof between 0.1 and 1.4 W/m°K and a thermal expansion coefficient TEC≦50ppm/°K, such as the material known under the name “SU8” (Shell Upon 8)produced by SOTEC MICROSYSTEMS. For example, the resist layer 18 has athickness of between 300 μm and 1 mm, preferably 500 μm.

[0035] Subsequently (FIG. 5), the resist layer 18 is defined so as toform an inlet reservoir 19 and an outlet reservoir 20. In particular,and as shown in the top view of FIG. 6, wherein the channels 3 arerepresented by dashed lines, the outlet reservoir 20 is formed as anextension of the outlet opening 16 b (and thus is connected to the endsof the channels 3 close to the sensing electrode 12) and encompasses thesensing electrode 12. The inlet reservoir 19 is formed, instead, as anextension of the inlet opening 16 a, and is thus connected to theopposite ends of the channels 3. Preferably, the reservoirs 19, 20 havea length (in a direction perpendicular to the plane of FIG. 5) ofapproximately 6 mm; the inlet reservoir 19 has a width (in a horizontaldirection in FIG. 5) of between 300 μm and 1.5 mm, preferablyapproximately 1 mm, so as to have a volume of at least 1 mm³, and theoutlet reservoir 20 has a width of between 1 and 4 mm, preferably ofapproximately 2.5 mm.

[0036] Next (FIG. 7), using as masking layer the resist layer 18 and theprotective layer 15, access trenches 21 a and 21 b are formed in thesemiconductor body 2 by performing a trench etching. In particular, theaccess trenches 21 a and 21 b extend aligned to the inlet and outletopenings 16 a, 16 b, from the surface 4 as far as the channels 3, so asto connect the channels 3 to one another in parallel, as well as to theinlet reservoir 19 and the outlet reservoir 20.

[0037] Finally, the exposed portion of the protective layer 15 isremoved, so as to expose the sensing electrode 12 again (FIG. 8), andthe wafer 1 is cut into dice to obtain a plurality of microreactors.

[0038] According to a different embodiment, the inlet and outletreservoirs are formed in a photosensitive dry-resist layer. In thiscase, the access trenches can be made before applying thephotosensitive, dry resist layer.

[0039] According to an implementation of this embodiment, wherein partscorresponding to those of the first embodiment are designated by thesame reference numbers, the process starts from a wafer 1, as shown inFIG. 2, comprising the semiconductor body 2, in which the buriedchannels 3 have already been formed. The first insulating layer 5, theheating element 10, the contact regions 11, the sensing electrode 12,the second insulating layer 13, and the protective layer 15 are alsoalready formed on the semiconductor body 2.

[0040] Subsequently (FIG. 9), using a special masking layer (not shown),the protective layer 15, the second insulating layer 13, the firstinsulating layer 5, and the semiconductor body 2 are etched to forminlet openings 27 a and outlet openings 27 b at the ends of the buriedchannels 3. In practice, the inlet opening 27 a of FIG. 9 corresponds tothe opening 16 a and the trench 21 a of FIG. 7, and the outlet opening27 b of FIG. 9 corresponds to the opening 16 b and the trench 21 b ofFIG. 7. If so required, the wafer 1 may be planarized.

[0041] Subsequently (FIG. 10), a resist layer 28 is applied. Here theresist layer 28 is made of a photosensitive dry resist, of the typecurrently used for printed circuits, wherein the photosensitive dryresist, supplied in rolls of various sizes and thicknesses, is appliedto the base coated with a copper layer, and is then laminated andthermocompressed. According to the invention, preferably aphotosensitive dry resist layer is used of an opposite type with respectto the protective layer 15 (here negative) having a thickness of between500 μm and 1 mm, which is made to adhere to the wafer 1 by lamination ata temperature of 105-118° C. and is cut according to the externalprofile of the wafer 1.

[0042] The resist layer 28 is then exposed (using a special mask),developed and etched so as to form the inlet reservoir 19 and the outletreservoir 20, thus obtaining the structure shown in FIG. 11. Finally,the uncovered portion of the protective layer 15 is removed so as toexpose the sensing electrode 12 again (FIG. 12).

[0043] The advantages of the described process and device are thefollowing. First, an integrated microreactor formed in a single piecemay be obtained, without bonding two wafers of silicon and/or glasstogether. The process involves steps that are usual in microelectronics,with decidedly lower costs than the current ones. The process ismoreover far from critical, affords high productivity, and does notrequire the use of materials (such as “glass frit”) which are difficultto use on account of their deformability. The method of operation of thedevice is as follows according to one embodiment of the invention. Theburied channels 3 function as a reactor cavity. A reactive fluid isintroduced into the inlet reservoir 19 and thence into the buriedchannels 3 via the access trench 21 a. This may be accomplished bycapillary action or by appropriate air pressure, or other acceptabletechniques. In the case of a PCR operation, the fluid is heated andcooled repeatedly according to specific parameters, which parameters maybe custom for each particular applications and fluid type. The settingof such parameters is within the skill of those in the art. The heatingis accomplished by the use of the heating element 10 as describedherein. The cooling step may be carried out by removing the heat andpermitting the fluid to cool towards the ambient. Cooling may beaccelerated by the use of a heat sink attached in a known manner to thesemiconductor body 2. Other cooling means may be employed asappropriate, for example, a cooling fan or by the circulation of aliquid coolant.

[0044] At the conclusion of the heating and cooling cycles the fluid isremoved from the buried channels 3 via the access trench 21 b, into theoutlet reservoir 20, by the application of air pressure, or by othermeans as appropriate. In some cases the fluid may be removed from theoutlet reservoir 20 for further processing. In one embodiment, thesensing electrode 12 is employed to detect a desired product of thereaction process in the fluid. This detection process is within theskill of those practiced in the art, and so will not be described indetail.

[0045] Having the sensor electrode 12 in the same semiconductorsubstrate and adjacent to the channel 3 is advantageous for certaintypes of such processes. Of course, other process sequences do notemploy such a sensor 12 and it does not need to be used in allembodiments of the invention.

[0046] Finally, it is clear that numerous variations and modificationsmay be made to the process and to the microreactor described andillustrated herein, all falling within the gist of the invention, asdefined in the attached claims. For example, the type of resist used forforming the resist layer and the protective layer may be different fromthe ones described herein. For instance, the protective layer 15 may bemade with a negative, instead of positive, resist or with anotherprotective material resistant to the etching of the resist layer and ofthe silicon, and selectively removable with respect to the secondinsulating layer 13; and the resist layer may be made with a positiveresist, instead of a negative one. Instead of a plurality of buriedchannels, it is possible to make a single buried channel of appropriatedimensions, for example applying the technique described in theaforementioned European Patent Application 99830206.1 and time-etchingthe silicon of the semiconductor body 2 extending between the buriedchannels 3 so as to form a single cavity having a width equal to that ofthe trenches 21 a, 21 b or of the openings 27 a, 27 b. In addition, inthe second embodiment, the resist layer 28 may be replaced by twolayers, the bottom layer having a function of support for the top one.

[0047] From the foregoing it will be appreciated that, although specificembodiments of the invention have been described herein for purposes ofillustration, various modifications may be made without deviating fromthe spirit and scope of the invention. Accordingly, the invention is notlimited except as by the appended claims.

1. An integrated microreactor comprising: a semiconductor material bodyhaving a surface; a buried channel extending in said semiconductormaterial body at a distance from said surface, and having a first and asecond ends; first and second trenches extending from said surfacerespectively as far as said first and second ends of said buriedchannel, and being in fluid connection with said buried channel; and areservoir region, extending above said surface and defining a first anda second reservoirs connected to said first and second trenches.
 2. Theintegrated microreactor of claim 1, wherein said first and secondreservoir have, in cross section, larger areas than said first andsecond trenches.
 3. The integrated microreactor according to claim 1,wherein said second reservoir has a larger area than said firstreservoir, and said integrated microreactor comprises a sensingelectrode structure extending above said surface and inside said secondreservoir.
 4. The integrated microreactor according to claim 1 furthercomprising a heating element arranged between said surface and saidreservoir region, above said buried channel.
 5. The integratedmicroreactor according to claim 4, further comprising an insulatingmaterial region extending between said surface and said reservoir regionand surrounding said heating element.
 6. The integrated microreactoraccording to claim 5, further comprising a protective region arrangedbetween said insulating material region and said reservoir region. 7.The integrated microreactor according to claim 6, wherein the reservoirregion is of a first resist and the protective region is of a secondresist, and in that one of said first and second resists is of anegative type, and the other of said first and second resists is of apositive type.
 8. The integrated microreactor according to claim 1,wherein the reservoir region is of a first resist.
 9. The integratedmicroreactor according to claim 8 wherein said first resist is SU8. 10.The integrated microreactor according to claim 8, wherein said firstresist is a photosensitive dry resist.
 11. A structure comprising: asemiconductor material body; a buried channel formed in thesemiconductor material body and at a distance from the surface of thesemiconductor material body. a first reservoir, formed on the surface ofthe semiconductor material body; a first trench, formed on thesemiconductor material body, extending from the first reservoir to afirst end of the buried channel; a second trench formed on thesemiconductor material body, extending from the surface of thesemiconductor material body to a second end of the buried channel; and aheating element, formed on the semiconductor material body adjacent tothe buried channel.
 12. The structure of claim 11, further comprising asecond reservoir, formed on the surface of the semiconductor materialbody, where the second trench extends from the second reservoir on thesurface of the semiconductor material body to a second end of the buriedchannel.
 13. The structure of claim 11, further comprising a sensingelectrode structure, formed on the semiconductor material body.
 14. Thestructure of claim 12, further comprising a sensing electrode structure,formed on the semiconductor material body and inside the secondreservoir.
 15. A process for the fabrication of an integratedmicroreactor, comprising: forming a semiconductor material body having asurface and a buried channel extending at a distance from said surfaceand having first and second ends; forming first and second trenchesextending from said surface as far as, respectively, said first and saidsecond ends of said buried channel and being in fluid connection withsaid buried channel; and above said surface, forming first and secondreservoirs respectively connected to said first and second trenches in areservoir layer of a first resist.
 16. The process according to claim15, wherein, before said step of forming first and second reservoirs,the step is carried out of forming a heating element surrounded by aninsulating layer and extending above said surface, over said buriedchannel.
 17. The process according to claim 16, wherein said step offorming first and second reservoirs is carried out before said step offorming first and second trenches.
 18. The process according to claim17, wherein, before said step of forming first and second reservoirs,the following step is carried out: forming a protective layer above saidsurface; and, after said step of forming first and second reservoirs,the following steps are carried out: selectively removing saidprotective layer as far as said surface, above said ends of said buriedchannel, to form first and second openings; and digging said first andsaid second trenches, in an aligned way to said first and secondopenings.
 19. The process according to claim 18, wherein said protectivelayer comprises a second resist, and one of said first and secondresists is of a negative type, and the other of said first and secondresists is of a positive type.
 20. The process according to claim 15,wherein said first resist is SU8.
 21. The process according to claim 15,wherein said step of forming first and second reservoirs is carried outafter said step of forming first and second trenches.
 22. The processaccording to claim 21, wherein, before said step of forming first andsecond reservoirs, the following steps are carried out: forming aprotective layer above said surface; selectively removing saidprotective layer as far as said surface, above said ends of said buriedchannel, to form first and second openings; and digging said first andsecond trenches in an aligned way to said first and second openings. 23.The process according to claim 15, wherein said first resist is aphotosensitive dry resist.
 24. The process according to claim 19,wherein said step of forming first and second reservoirs comprises thefollowing steps: applying a reservoir layer by lamination andthermocompression; and selectively removing said reservoir layer.
 25. Amethod, comprising: introducing a fluid from a first reservoir into afirst trench, the first reservoir and first trench being integrated in asemiconductor body; introducing the fluid from the first trench into aburied channel, the buried channel extending in a semiconductor materialbody at a distance from a surface of the semiconductor material body,the first trench extending from the reservoir on the surface of thesemiconductor material body to a first end of the buried channel;heating the fluid within the buried channel; and cooling the fluidwithin the buried channel.
 26. The method of claim 25 wherein theheating step is performed by: passing an electric current through aheating element arranged in the semiconductor material body on top ofthe buried channel.
 27. The method of claim 25, further including thestep of extracting the fluid from the buried channel into a secondreservoir via a second trench, the second reservoir and second trenchbeing integrated in the semiconductor body, the second trench extendingfrom the second reservoir on the surface of the semiconductor materialbody as far as a second end of the buried channel.
 28. The method ofclaim 25, further including the step of detecting a desired productwithin the fluid, where the detection step is performed by the use of asensing electrode structure, the sensing electrode structure beingintegrated in the semiconductor material body and in contact with thefluid.
 29. The method of claim 24 wherein the first and secondreservoirs are formed in, and defined by a resist layer formed on thesurface of the semiconductor material body.
 30. The method according toclaim 25 further including: repeating the heating and cooling steps aplurality of times to achieve a desired reaction in biological matterwithin the fluid.
 31. The method according to claim 25, wherein thecooling step is carried out by: terminating the heating of the fluid;and permitting the fluid to cool towards the ambient.
 32. The methodaccording to claim 25, wherein the cooling step is carried out by:terminating the heating of the fluid; and drawing heat from the fluidusing a heat transfer mechanism.